The long term goal of our research is to determine the role of TcNGA parameter estimates of liver function and their relationship to liver disease, both from a diagnostic and prognostic viewpoint. We plan to evaluate the usefulness of TcNGA as a quantitative measure of liver function in four areas: 1) prognosis in liver disease, 2) therapeutic effect in liver disease, 3) classification of disease presence and disease category, and 4) regional versus global estimation of liver function. Aims, 1, 2 and 3 will be accomplished using modern statistical analysis. Using the Cox regression models, information on variables associated with prognosis and therapeutic effect in liver disease can be obtained, as well as a more precise estimation of therapy-dependent prognosis in the individual patient. With the discriminant analysis method, classification of disease presence and disease category can be accomplished. Aim 4 will be a preliminary evaluation using planar, SPECT, and PET NGA imaging techniques. This will address the question of whether regional estimates of liver function add significant prognostic or therapeutic information. It will also address the advantages and disadvantages of PET versus SPECT versus planar NGA kinetic modeling. In addition, the 14C-aminopyrine breath test and the endogenous ligand assay will be performed, and when possible, we will obtain and assay liver biopsy samples for determination of hepatic binding protein concentration. These values will be correlated with the NGA functional parameter estimates.